System and Method for Eyelid Simulation

ABSTRACT

A system and method of treating hyperactivity of an eyelid closing muscle in a subject after facial nerve paralysis includes providing a stimulation system and selectively stimulating eyelid opening muscle(s) or innervating nerves, eyelid opening reflexes, or eyelid opening reflexes in non-muscular tissue, using the stimulation system, without substantially activating the eyelid closing muscle. The system and method evokes eyelid movement in the subject.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Provisional PatentApplication No. 61/570,409 filed Dec. 14, 2011, the disclosure of whichis incorporated by reference herein in its entirety.

TECHNICAL FIELD

The invention generally relates to stimulation methods and systems and,more particularly, the invention relates to eyelid stimulation.

BACKGROUND ART

There are various articles describing eyelid opening and closingmechanisms and the related eyelid structures involved. For example, onearticle describes the stretching of the Mueller muscle which results ininvoluntary contraction of the levator muscle (K. Matsuo, Ophthal PlastReconstr Surg, 18(1), 2002 January, p. 5-10). Another article describesthe refined distribution of myelinated trigeminal proprioceptive nervefibers in Mueller's muscle as the mechanoreceptors to induce involuntaryreflexive contraction of the levator and frontalis muscles (S. Yuzuriha,K. Matsuo, C. Hirasawa, T. Moriizumi, J Plast Reconstr Aesthet Surg,62(11), 2009 November, p. 1403-1410). Another article describes thereflexive contraction of the levator palpebrae superioris muscle toinvoluntarily sustain the effective eyelid retraction through thetransverse trigeminal proprioceptive nerve on the proximal Mueller'smuscle, and its verification with evoked electromyography (R. Ban, K.Matsuo, Y. Osada, M. Ban M, S. Yuzuriha, J Plast Reconstr Aesthet Surg,63(1), 2010 January, p. 59-64). Another article describes the efferentand afferent innervations of Mueller's muscle related to the involuntarycontraction of the levator muscle, which is important for avoidinginjury during eyelid surgery (S. Yuzuriha, K. Matsuo, Y. Ishigaki, N.Kikuchi, K. Kawagishi, T. Moriizumi, Br J Mast Surg, 58(1), 2005January, p. 42-52). All of the above articles are hereby incorporated byreference in their entirety.

Some problems encountered with eyelid opening and closing mechanisms maybe caused by unilateral damage of the nerve fibers of the facial nerveor its nucleus which leads to peripheral facial paresis. In WesternEurope and the USA, the incidence of peripheral facial pareses isapprox. 20-35/100,000 inhabitants. Thus, facial paresis is a commondisease. In most cases and depending on the cause, peripheral paresisshows non-degenerative paresis (neurapraxia according to Seddon) so that80% of the cases show regeneration of the nerve under adequate therapy.95% of cases with central facial paresis show regeneration. In cases ofdegenerative paresis (axonotmesis, neurotmesis, mixed forms according toSeddon) caused by the destruction of nerve fibers, persistent defectsare observed after healing.

Persistent defects after healing are even observed in cases ofspontaneous regeneration or optimal and extensive surgicalreconstruction of the nerve in cases of nerve transsection and bridgingof the defect with neural transplants. Sprouting of the regeneratingaxons is observed at the site of the lesion even after reconstruction ofnerve continuity. At the same time, Wallerian degeneration of the entireaffected section of the nerve as far as the muscles is completed untilonly the Bungner's bands remain as Schwann cell conducting structures.The regenerating neurons with their sprouting axons grow accidentallyinto these bands of the individual nerve branches and are directed tothe peripheral mimic muscles. Individual axons perish and do not reachthe periphery, some accidentally reach their original target muscle,while others reach a completely different target muscle. Due to axonalcollateral sprouting, the most frequently observed effect issimultaneous sprouting to several target muscles, such as shown in FIGS.1A and 1B.

This leads clinically to simultaneous movement of several target muscles(a condition called synkinesis). Patients often complain aboutinvoluntary lid closure while moving the mouth, e.g., when eating.Simultaneous movement of antagonist muscles leads to the autoparalyticsyndrome: muscle forces cancel each other out and no movement isobserved clinically despite innervation. New research shows that notonly collateral sprouting but also terminal sprouting (such as shown inFIGS. 2A and 2B) of the regenerating axons directly at the neuromuscularend-plates causes uncoordinated muscle function. This explains why thepatients' quality of life is significantly limited even after surgicalreconstruction of the nerve. If the lesion is so extensive that theremaining peripheral part of the facial nerve is insufficient, or ifBungner's bands are fibrosed due to failed reinnervation and muscles areatrophied due to long term denervation of more than 3 to 5 years, thepatient can no longer be offered a nerve graft. Possible therapiesinclude dynamic muscle grafts, free nerve-muscle transplantation,implantation of upper lid weights or static suspensions. Functionalresults of these secondary procedures are even less satisfactory thanthe above mentioned nerve grafts. These procedures may, at best, restoremuscle tone, but facial expression remains very mask-like and thedynamic muscle suspensions allow only few and very mechanistic movementvectors to be reproduced.

There are basically three classes of symptoms in facial nerve paralysisthat may affect eyelid closure. First, a complete loss of the peripheralfacial nerve leads to a loss of muscle tone in the affected half of theface or of the area innervated by the lost peripheral facial nervebranch and the soft tissues of the face sag. Voluntary motor movement islost, and mimic muscles can no longer be moved. The inability to closethe eyelid indirectly leads to vision disorders since the eye waters andinflammation is possible. This hypo-eyelid-closure problem affects lessthan 20% of patients.

Second, a pronounced but synkinetic reinnervation leads to thesimultaneous movement of several target muscles. As mentioned above,patients may experience involuntary lid closure, e.g., while moving themouth, or simultaneous movement of antagonist muscles which leads to themuscle forces cancelling each other out. This disynergic-eyelid-closureproblem affects greater than 30% of patients.

Third, peripheral polyinnervation, central poly-activation or centralhypo-inhibition, may lead to an almost continuous contraction of amuscle, like in a tremor, spasm or spasmodic pathogenesis. Thishyperactivity of the musculus orbicularis oculi or hyper-eyelid-closureproblem affects greater than 30% of patients. There are some therapiesadapted for hyper-contractions of a muscle that may be used in eyelidclosure. These therapies focus on pathologically weakening thehyper-contracted or hyper-activated muscles that are involved in thetremor or spasm. For example, botulinum toxin may be injected incontracting muscles to temporarily damage nerve-muscle transfer of someof the synapses of the contracting muscles. Alternatively, somepercentage of nerve fibers innervating the contracting muscle, or somepercentage of the muscle fibers of the contracting muscle, may besurgically damaged.

SUMMARY OF EMBODIMENTS

In accordance with one embodiment of the invention, a method of treatinghyperactivity of an eyelid closing muscle in a subject includesproviding a stimulation system and selectively stimulating one or moreeyelid opening muscles or innervating nerves, using the stimulationsystem, without substantially activating the eyelid closing muscle,thereby evoking eyelid movement in the subject.

In accordance with another embodiment of the invention, a method oftreating hyperactivity of an eyelid closing muscle in a subject includesproviding a stimulation system and selectively stimulating one or moreeyelid opening reflexes in muscles, using the stimulation system,without substantially activating the eyelid closing muscle, therebyevoking eyelid movement in the subject.

In accordance with another embodiment of the invention, a method oftreating hyperactivity of an eyelid closing muscle in a subject includesproviding a stimulation system and selectively stimulating one or moreeyelid opening reflexes in non-muscular tissue, without substantiallyactivating the eyelid closing muscle, thereby evoking eyelid movement inthe subject.

In accordance with related embodiments, stimulating may includeelectrical stimulation, mechanical stimulation, and/or vibratorystimulation. The eyelid opening muscles may include levator muscleand/or frontal muscle. Stimulated levator muscle may include slow-twitchmuscle fibers and/or fast-twitch muscle fibers. Stimulating eyelidopening reflexes in muscles may include stimulating levator fast-twitchmuscle fibers to cause activation of mechanoreceptors in Mueller'smuscle and intermuscular connective tissues leading to an involuntarycontinuous contraction of levator slow-twitch muscle fibers. Stimulatingeyelid opening reflexes in muscles may include stimulating transversenerve fibers to induce involuntary contraction of levator muscle andMueller's muscle. Stimulating eyelid opening reflexes in muscles mayinclude stimulating sympathetic y efferent nerve fibers to increaseefferent sympathetic tone thereby increasing the rate of involuntarytonic contraction of the muscles. Movement may be opening or closing ofthe eyelid. When opening the eyelid, the opening may be caused byretraction of the eyelid against gravity and may be maintained byinvoluntary continuous contraction of the levator slow-twitch musclefibers as a result of proprioception. The eyelid movement may be causedby shortening a distal part of the Mueller muscle due to the increasedefferent sympathetic tone. Stimulating eyelid opening reflexes innon-muscular tissue may include stimulating I-a proprioceptive afferentnerve connecting a mechanoreceptor of intermuscular connective tissuesamong middle and distal Mueller's smooth muscle fibers with motornucleus to induce involuntary contraction of levator muscle andMueller's muscle. Stimulating eyelid opening reflexes in non-musculartissue may include stimulating intermuscular connective tissues amongmiddle and distal Mueller's smooth muscle fibers to induce reflexivecontraction.

In accordance with another embodiment of the invention, a stimulationsystem for treating hyperactivity of an eyelid closing muscle in asubject includes a processor having program code for generating at leastone stimulation parameter that is used to stimulate one or more eyelidopening muscles or innervating nerves of the subject, and a stimulatorconfigured to receive the stimulation parameter and to stimulate the oneor more eyelid opening muscles or innervating nerves based on thestimulation parameter. Alternatively, or in addition, the stimulationparameter may be used to stimulate one or more eyelid opening reflexesin muscles and/or may be used to stimulate one or more eyelid openingreflexes in non-muscular tissue.

In accordance with related embodiments, the stimulation system mayfurther include an activating switch, in communication with theprocessor, configured to generate a first signal. The processor hasprogram code for receiving the first signal and for generating the atleast one stimulation parameter based on the first signal. Theactivating switch may automatically activate the stimulation systembased on various sensed parameters or may manually activate the system.For example, the activating switch may be a sensing electrode configuredto detect activity of the eyelid closing muscle and/or the activatingswitch may be a manual activator operable by the subject. The processormay be configured to receive the first signal by inductive coupling,capacitive coupling, electromagnetic transmission, light coupling,vibratory coupling, mechanical coupling and/or acoustical coupling.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing features of the invention will be more readily understoodby reference to the following detailed description, taken with referenceto the accompanying drawings, in which:

FIG. 1A shows a diagram of normal somatotopic organization of facialinnervation and FIG. 1B shows the condition after lesion of the facialnerve;

FIG. 2A shows a diagram of a normal end-plate region on a muscle fiberand FIG. 2B shows a diagram of end-plates activated by several axons dueto terminal sprouting;

FIG. 3 shows a schematic illustration of Müller's muscle;

FIG. 4 shows a schematic illustration of the innervation of Müller'smuscle;

FIG. 5 shows a stimulation system for treating hyperactivity of aneyelid closing muscle according to embodiments of the present invention;and

FIG. 6 shows a process of treating hyperactivity of an eyelid closingmuscle according to embodiments of the present invention.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention is directed to a system and method of eyelidstimulation that selectively activates the eyelid opening muscle(s)(levator, levator palpebrae superioris muscle, and frontalis muscles)without activating the eyelid closing muscle(s). The activation mayinclude stimulation of one or more of the eyelid opening muscles orinnervating nerves, the eyelid opening reflexes in muscles, and/or theeyelid opening reflexes in non-muscular tissue. For example, the musclefibers or the innervating nerves of the levator muscle or the frontalismuscle may be stimulated. Alternatively, or in addition, the fast-twitchmuscle fibers of the levator muscle may be stimulated to causeactivation of mechanoreceptors in Mueller's muscle and intermuscularconnective tissues, leading to an involuntary, continuous contraction oflevator slow-twitch muscle fibers in order to induce the eyelid movementin patients. Alternatively, or in addition, the transverse nerve fibersmay be stimulated to induce involuntary contraction of both the levatormuscle and Mueller's muscle in order to induce the eyelid movement inpatients. Alternatively, or in addition, the sympathetic y efferentnerve fibers, or via the superior cervical ganglion, may be stimulatedto increase efferent sympathetic tone to increase the rate ofinvoluntary tonic contraction of the muscle(s) causing the eyelidmovement in patients. Alternatively, or in addition, the I-aproprioceptive afferent nerve connecting the mechanoreceptor of theintermuscular connective tissues among the middle and distal Mueller'ssmooth muscle fibers with the motor nucleus may be stimulated to induceinvoluntary contraction of both the levator muscle and Mueller's muscle.Alternatively, or in addition, the intermuscular connective tissuesamong the middle and distal Mueller's smooth muscle fibers may bestimulated to induce reflexive contraction of the eyelid openingmuscles. In all cases, the stimulation may be electrical stimulation,mechanical stimulation and/or vibratory stimulation of the muscles,nerves, and/or reflexes.

In patients with synkinetic reinnervation after facial nerve paralysis,the synkinetic reinnervation and polyinnervations may lead to an almostcontinuous contraction of a muscle, exhibiting symptoms like in atremor, spasm or spasmodic pathogenesis. This condition is not very wellunderstood and standard therapies and procedures focus on the symptomsof the continuous contraction of the muscle. The consensus is thatstimulation of any part of the patient's affected facial nerve systemshould be avoided so that the symptoms are not made worse. Instead,standard therapies focus on pathologically weakening thehyper-contracted or hyper-activated muscles involved in the tremor orspasm. In patients with eyelid closure issues, the general belief isthat the tremor-like, spasm-like, or spasmodic-like pathogenesis is atremor or spasm of all muscles attached to the eyelid (e.g., openers,closers, tensors) where activation of some part of the tremor-,spasmodic-system bears a high risk of increasing the contraction ofmuscles involved in the tremor or spasm.

Embodiments of the present invention, however, discovered thatselectively focusing stimulation on the contraction of muscles openingor elevating the eyelid without causing any contraction of the eyelidclosing muscles, overcame these tremor-like symptoms. This was due tofact that the net closing force of the tremor- or spasmodic-likeactivated closing muscle(s) is overcome and compensated by the netopening force of one or more of the eyelid opening muscles. Since theeye closing muscles are innervated by a nerve (facialis) different thanthe eye opening muscles (trigeminus), embodiments of the presentinvention focus on activating the eyelid opening muscles(s) withoutactivating the eyelid closing muscle(s). For example, the selectivestimulation of one or more eyelid opening muscles or innervating nerves,eyelid opening reflexes in muscles, and/or eyelid opening reflexes innon-muscular tissue may compensate for the problem ofhyper-eyelid-closure or hyperactivity of the musculus orbicularis oculi.Currently, there is no way of surgically or pharmaceutically activatingantagonists of hyper-contracting eyelid closing muscles to compensatefor the hyper-closure by appropriate contraction of eyelid openingmuscle(s). Thus, the selective stimulation of eyelid opening musclesusing electrical, mechanical and/or vibratory methods, according toembodiments of the present invention, provides a valuable treatmentsolution for patients with these kinds of problems.

There are several eyelid opening muscles that help to open the eyelid,the levator muscle, levator palpebrae superioris muscle, and frontalismuscles. The levator muscle is innervated by the central caudal nucleusof the oculomotor nuclear complex and is a skeletal muscle whichoriginates from the orbital bone and transforms into the levatoraponeurosis. The deep expansion of this aponeurosis inserts into theanterior surface of the tarsus, the middle expansion into the pretarsalorbicularis oculi muscle, and the superficial expansion becomes theorbital septum. Thus, contraction of the levator muscle retracts thetarsus, the pretarsal orbicularis oculi muscle and skin, and the lateralorbital fat pad by means of the expansions of the levator aponeurosis.As shown in FIG. 3, the Mueller muscle, on the other hand, which isinnervated by the sympathetic efferent via the superior cervicalganglion, is a smooth muscle, which originates from the undersurface ofthe levator muscle and inserts onto the superior border of the tarsus.Because the levator muscle fibers do not surround the Mueller musclefibers and lie in series with them, contraction of the levator musclestretches the Mueller muscle along with the levator aponeurosis.

FIG. 4 shows the gross anatomy of the innervations of Mueller's muscle.A fine transverse nerve is accompanied by the peripheral arcade (arrow),and other nerves that run between the distal portion of the levatormuscle and the proximal portion of Mueller's muscle (arrow heads) passthrough the lacrimal gland to join the lacrimal nerve. In FIG. 4, Tindicates the tarsus; M, Mueller's muscle; L, levator muscle; LH,lateral horn (turned up); PF, preaponeurotic fat; LG, lacrimal gland;SON, supraorbital nerve; LN, lacrimal nerve; ZFN, zygomatico-facialnerve.

In some cases, denervated muscle fibers may be innervated by more thanone nerve fiber. In this case, the action potentials for contractionarrive from nerve fibers originally innervating muscle fibers fordifferent functions (e.g., the antagonistic muscle). Thispolyinnervation—which may be due to the overlapping or disturbance ofcentral projection areas of peripheral muscles in the brain—causesactivation of muscle fibers during many more activities or functionsthan originally desired for a certain muscle. This situation may lead toan almost continuous contraction of the muscle (e.g., like in a tremoror spasm or spasmodic pathogenesis) in some cases. In situations such asthis, a patients' quality of life may be significantly limited evenafter surgical reconstruction of the nerve.

FIGS. 5 and 6 show a stimulation system 10 and method 100, respectively,for treating hyperactivity of an eyelid closing muscle according toembodiments of the present invention. The stimulation system 10 includesone or more stimulators 15 and a processor 20, in communication with thestimulator 15, which may include a pulse generator. As mentioned above,the stimulation may be electrical, mechanical, and/or vibratorystimulation. For example, the stimulator may be a stimulating electrode,e.g., a 1 mm stimulating electrode.

In some embodiments, the stimulation system 10 further includes anactivating switch 25 that activates the stimulation system. Theactivating switch 25 may automatically activate the stimulation system10 based on various sensed parameters or may manually activate thesystem, e.g., through the use of a manual activator, operable by thesubject, e.g., a switch or toggle. For example, the activating switch 25may be a sensing electrode configured to sense the activity of an eyelidclosing muscle and the stimulator 15 is configured to stimulate theeyelid opening muscles or innervating nerves, the eyelid openingreflexes in muscles, and/or the eyelid opening reflexes in non-musculartissue, based on the sensed activity. The stimulator(s) 15 may be placednear or in contact with the eyelid opening muscles or innervatingnerves, the eyelid opening reflexes in muscles, and/or the eyelidopening reflexes in non-muscular tissue.

Embodiments of the present invention may be totally or partiallyimplanted in the subject. For example, the stimulator may include ahousing that can be very small with all of the implant's electroniccomponents contained in a robust and compact hermetically sealed case.Energy and necessary information may be inductively or opticallytransferred through the skin of the subject. This can be achieved byeither enclosing the electronic circuitry inside a metallic case with asecondary coil placed aside or around the case. Similarly, this may beachieved by enclosing the electronic circuitry and a secondary coilinside a dielectric case.

Once the stimulation system is activated (step 110), the processor 20generates at least one stimulation parameter that is used to stimulatethe eyelid opening muscles, nerves, and/or reflexes (step 120). Forexample, the stimulation parameter may be a biphase current pulse, andthe biphase current pulse may have a duration of about 0.001 ms to 50ms, in most subjects from about 0.1 msec to 5 msec, and a magnitude inthe range of about 0.05 mA to 20 mA, in most subjects from about 0.5 mAto 5 mA. The stimulation parameter may be a frequency and/or amplitudeof vibration, and the stimulator may be a vibration generator, such as apiezoelectric actuator, an electrodynamic actuator and/or a mechanicalactuator.

The stimulation parameter from the processor 20 is received by the oneor more stimulators 15, and the stimulator stimulates the eyelid openingmuscles or innervating nerves, the eyelid opening reflexes in muscles,and/or the eyelid opening reflexes in non-muscular tissue, based on thestimulation parameter (step 130).

Some embodiments of the processor 20 may be implemented as hardware,software (e.g., a computer program product), or a combination of bothsoftware and hardware. For example, embodiments may be implemented as acomputer program product for use with a computer system. Suchimplementation may include a series of computer instructions or programcode fixed either on a tangible medium, such as a computer readablemedium (e.g., a diskette, CD-ROM, ROM, or fixed disk) or transmittableto a computer system, via a modem or other interface device, such as acommunications adapter connected to a network over a medium. The mediummay be either a tangible medium (e.g., optical or analog communicationslines) or a medium implemented with wireless techniques (e.g.,microwave, infrared or other transmission techniques). The series ofcomputer instructions may embody all or part of the functionalitypreviously described herein with respect to the processor. Those skilledin the art should appreciate that such computer instructions may bewritten in a number of programming languages for use with many computerarchitectures or operating systems. Furthermore, such instructions maybe stored in any memory device, such as semiconductor, magnetic, opticalor other memory devices, and may be transmitted using any communicationstechnology, such as optical, infrared, microwave, or other transmissiontechnologies. It is expected that such a computer program product may bedistributed as a removable medium with accompanying printed orelectronic documentation (e.g., shrink wrapped software), preloaded witha computer system (e.g., on system ROM or fixed disk), or distributedfrom a server or electronic bulletin board over the network (e.g., theInternet or World Wide Web).

While the invention has been described in connection with specificembodiments thereof, it will be understood that it is capable of furthermodification. This application is intended to cover any variation, uses,or adaptions of the invention and including such departures from thepresent disclosure as come within known or customary practice in the artto which invention pertains.

What is claimed is:
 1. A method of treating hyperactivity of an eyelidclosing muscle in a subject, the method comprising: providing astimulation system; and selectively stimulating one or more eyelidopening muscles or innervating nerves, using the stimulation system,without substantially activating the eyelid closing muscle, therebyevoking eyelid movement in the subject.
 2. The method according to claim1, wherein the stimulating includes electrical stimulation, mechanicalstimulation, vibratory stimulation, or combinations thereof.
 3. Themethod according to claim 1, wherein the eyelid opening muscles includelevator muscle, frontal muscle, or a combination thereof.
 4. The methodaccording to claim 3, wherein the stimulated levator muscle includes atleast one of slow-twitch muscle fibers and fast-twitch muscle fibers. 5.A stimulation system for treating hyperactivity of an eyelid closingmuscle in a subject, the system comprising: a processor having programcode for generating at least one stimulation parameter that is used tostimulate one or more eyelid opening muscles or innervating nerves ofthe subject; and a stimulator configured to receive the stimulationparameter and to stimulate the one or more eyelid opening muscles orinnervating nerves of the subject based on the stimulation parameter. 6.The system according to claim 5, further comprising: an activatingswitch configured to generate a first signal, wherein the processor isin communication with the activating switch and the processor hasprogram code for receiving the first signal and for generating the atleast one stimulation parameter based on the first signal.
 7. The systemaccording to claim 6, wherein the activating switch is a manualactivator operable by the subject.
 8. The system according to claim 6,wherein the activating switch is a sensing electrode configured todetect activity of the eyelid closing muscle.
 9. A method of treatinghyperactivity of an eyelid closing muscle in a subject, the methodcomprising: providing a stimulation system; and selectively stimulatingone or more eyelid opening reflexes in muscles, using the stimulationsystem, without substantially activating the eyelid closing muscle,thereby evoking eyelid movement in the subject.
 10. The method accordingto claim 9, wherein the stimulating includes electrical stimulation,mechanical stimulation, vibratory stimulation, or combinations thereof.11. The method according to claim 9, wherein stimulating eyelid openingreflexes in muscles includes stimulating levator muscle fast-twitchmuscle fibers to cause activation of mechanoreceptors in Mueller'smuscle and intermuscular connective tissues leading to an involuntarycontinuous contraction of levator slow-twitch muscle fibers.
 12. Themethod according to claim 11, wherein the movement is opening of theeyelid, and the opening is caused by retraction of the eyelid againstgravity and is maintained by involuntary continuous contraction of thelevator slow-twitch muscle fibers as a result of proprioception.
 13. Themethod according to claim 9, wherein stimulating eyelid opening reflexesin muscles includes stimulating transverse nerve fibers to induceinvoluntary contraction of levator muscle and Mueller's muscle.
 14. Themethod according to claim 9, wherein stimulating eyelid opening reflexesin muscles includes stimulating sympathetic y efferent nerve fibers toincrease efferent sympathetic tone thereby increasing rate ofinvoluntary tonic contraction of the muscles.
 15. The method accordingto claim 14, wherein the eyelid movement is caused by shortening adistal part of the Mueller muscle due to the increased efferentsympathetic tone.
 16. A stimulation system for treating hyperactivity ofan eyelid closing muscle in a subject, the system comprising: aprocessor having program code for generating at least one stimulationparameter in order to stimulate one or more eyelid opening reflexes inmuscles of the subject; and a stimulator configured to receive thestimulation parameter and to activate the one or more eyelid openingreflexes in muscles of the subject based on the stimulation parameter.17. A method of treating hyperactivity of an eyelid closing muscle in asubject, the method comprising: providing a stimulation system; andselectively stimulating one or more eyelid opening reflexes innon-muscular tissue, using the stimulation system, without substantiallyactivating the eyelid closing muscle, thereby evoking eyelid movement inthe subject.
 18. The method according to claim 17, wherein thestimulating includes electrical stimulation, mechanical stimulation,vibratory stimulation, or combinations thereof.
 19. The method accordingto claim 17, wherein stimulating eyelid opening reflexes in non-musculartissue includes stimulating I-a proprioceptive afferent nerve connectinga mechanoreceptor of intermuscular connective tissues among middle anddistal Mueller's smooth muscle fibers with motor nucleus to induceinvoluntary contraction of levator muscle and Mueller's muscle.
 20. Themethod according to claim 17, wherein stimulating eyelid openingreflexes in non-muscular tissue includes stimulating intermuscularconnective tissues among middle and distal Mueller's smooth musclefibers to induce reflexive contraction.
 21. A stimulation system fortreating hyperactivity of an eyelid closing muscle in a subject, thesystem comprising: a processor having program code for generating atleast one stimulation parameter in order to stimulate one or more eyelidopening reflexes in non-muscular tissue of the subject; and a stimulatorconfigured to receive the stimulation parameter and to activate the oneor more eyelid opening reflexes in non-muscular tissue of the subjectbased on the stimulation parameter.